The large-scale gene analysis to develop the tailor-made prevention of osteoporosis

本研究以日本女性人群为研究对象，研究了维生素D受体、转化生长因子-β、骨钙素、亚甲基四氢叶酸还原酶、细胞色素P450 19、细胞色素P1A1和骨钙素基因的单核苷酸多态对骨密度的影响，以及这些多态与生活方式因素对骨密度的影响。作为日本基于人口的骨质疏松症(JPOS)基线研究的一部分，从三个选定的城市中每个城市的5岁年龄分层人口(15-79岁)中随机选择了50名妇女。在基线时使用DXA测量腰椎、髋部和前臂远端的骨密度，并在基线三年后进行随访研究。生活方式因素的信息通过问卷收集并在访谈中进行随访。采用聚合酶链式反应-限制性片段长度多态性分析和TaqMan等位基因鉴别分析。在基线时，对1340名女性进行了分析。每种基因型与基线骨密度或任何骨骼部位骨密度变化之间没有关联。我们发现，每日牛奶摄入量与某些骨骼部位的基线骨密度显著相关，但仅限于VDR基因中CDX-2结合部位的GG基因型受试者。JPOS研究发现，绝经后妇女纳豆摄入量与骨密度变化率之间存在显著的正相关关系。我们发现，在绝经后妇女中，纳豆摄入量与股骨颈骨密度的CYP19和COMT基因多态之间存在显著的交互作用。此外，骨质疏松症和骨量减少的患病率在不同的CYP19基因型之间是不同的。结论：每个多态性单独对日本女性的骨密度没有实质性的影响。然而，这些多态可能会对具有特定生活方式因素的女性产生一些影响。目前，我们正在研究其他候选基因对骨密度的影响，并寻找与骨形成相关的新的多态性。

Using a large-scale representative sample of the Japanese female population, we examined the effects of single nucleotide polymorphisms in the VDR, TGF-β, Osteocalcin, MTHFR, CYP19, CYP1A1 and COMT gene on bone mineral density (BMD), and the interactions between these polymorphisms and lifestyle factors on BMD. Fifty women were randomly selected from each of the 5-year age-stratified populations (15-79 years) in each of three chosen municipalities as a part of the Japanese population-based osteoporosis (JPOS) baseline study. BMD at the lumbar spine, hip and distal forearm were measured using DXA at baseline, and again in a follow-up study conducted three years after the baseline.Information on lifestyle factors was collected in a questionnaire and followed up in interviews. The polymorphisms were determined by the PCR-RFLP method and a TaqMan allelic discrimination assay. At baseline, 1,340 women were analyzed. There was no association between each genotype and the baseline BMD or the change in BMD at any of the skeletal sites. We found significant associations between daily milk consumption and baseline BMD at some skeletal sites, but only in subjects with GG genotype within a binding site of Cdx-2 in the VDR gene. There were significant positive associations between the natto intake and the rates of changes in BMD in postmenopausal women of JPOS study. We found significant interactions between the natto intake and CYP19 and COMT polymorphisms on BMD at femoral neck in postmenopausal women. In addition, the prevalence of osteoporosis and osteopenia was different between the genotypes of CYP19.In conclusion, each polymorphism alone did not have substantial effect on BMD in Japanese women. However, these polymorphisms might have some effect in women with specific lifestyle factors. Currently, we are studying the effects of other candidate genes on BMD and searching new polymorphisms associated with bone formation.